Semi-solid extruded tablets for personalized pediatric use: Development, Quality control and In-Vitro Assessment of...

Drug compounding is a common practice in pediatric medication due to limited availability of appropriate dosage forms for children. Semi-solid extrusion (SSE) as a way of 3D printing has shown a substantial potential in personalized medicine for pediatric patients. However, manufacturing tablets through 3D printing is a slow process and might be a bottleneck when many personalized dosages are needed for pediatric use. Here, we use a simplified SSE printing approach for preparing propranolol, spironolactone, and prednisolone tablets (n = 144 of each) with different dosages. The quality control approach for the tablets included the development of HPLC methods for each drug based on their physicochemical properties and investigation of mass and content uniformity, stability, and dissolution. The average dosing accuracy showed good mass uniformity. All the formulations showed an appropriate homogeneity (AV<15) and stability up to 9 months. Dissolution results of the tablets were in compliance with acceptance criteria (USP) for immediate release dosage forms, i.e., 80% of drug released within 45 min. The osmolality of placebo, propranolol, spironolactone, and prednisolone tablets were 86, 81, 78, and 75 mOsm/kg, respectively. These osmolality values were well below the recommended osmolality of pediatric formulations, i.e., < 450 mOsm/kg. Finally, drug recovery tests via nasogastric tube (NGT) were performed with different reconstitution volumes and temperatures. The drug losses varied between 4-36%. The findings of this study suggest that a simplified SSE printing approach is a promising method for manufacturing personalized medicines and can be used to accurately produce tailor-made dosage forms for pediatric patients.